Syphilis, a stigmatized and greatly feared disease by the society because of the pain and the disfigurement that followed, was the first identified sexually transmitted infections (STIs).
Syphilis, the name itself had originated from the work of Girolamo Fracastoro, a poet and a medical personality, who wrote ‘Syphilis Sive Morbus Gallicus’. The origin of syphilis was under the subject of various debates before the discovery of the bacterium Treponema pallidum.
Until the early 20th century, one of the very popular hypothesis states that the navigators in Columbus fleet, on their return from the New World had brought the disease back on their return in 1493. For the affected individuals, if the disease did not kill them, the cure mostly certainly did. In an effort to treat the disease, throughout history, different therapeutic agents were used that included plants such as guaiac tree (lat. Guaiacum Officinale), the use of mercury and bismuth salts. Interestingly, a German scientist named Paul Ehrlich, who received the Nobel Prize in Physiology and medicine in 1908 discovered arsphenamine (Salvarsan) but later the safer drug used for the treatment of syphilis was Neosalvarsan.
The seriousness of the disease led to a national syphilis control campaign in 1938 and the therapy usually included prolonged injections of arsenicals, which was later replaced with the use of penicillin after 1940 for all stages of syphilis thus reducing the incidence of the disease and the rate of mortality. From 1944 to 1954, the cases of syphilis decreased by more than 75% and by 1975, the rate of syphilis had declined by nearly 90%.
Syphilis as a study project
The research on syphilis historically has been considered a special disease as an STD with no effective treatment available for years. The syphilis study post second world war II continued without any ethical standards for several decades. One of the notable projects initiated by the US Public Health Service was the syphilis study with the aim of monitoring the natural course of the disease when left untreated. This study involved adults who were deliberately inoculated with the infectious material between 1946 and 1948 in Guatemala and between 1932 and 1972 in Tuskegee. Even with the use of penicillin therapy in the 1940s, the participants of the project were not administered treatment until the 1970s.
Since the high rates of infection in the period of World War II, a great progress was made to effectively manage the disease. However, the Centers for Disease Control and Prevention data from 2014 indicate an increase in the new cases of syphilis. After the World War II, and in the late 1980s and early 1990s, the most affected population changed from heterosexual epidemic to MSM (men having sex with men). Also, the number of congenital syphilis cases also appeared to be on the rise.
Incidence
Syphilis is still prevalent in our global society and according to the health officials, 50,000 cases of syphilis were reported in the United States in 2013 of which 17,000 cases are of primary and secondary stage and 75% were detected among men with the same sex partner. In 2017, new cases of syphilis were estimated at 101,567 compared to the 39,782 cases of HIV infection in 2016 according to Centers for Disease Control and Prevention (CDC). With the increasing rates of newly diagnosed cases, the need for syphilis screening for at-risk individuals was reaffirmed by the United States Preventative Health Services Task Force. However, the primary care physicians were unable to accurately determine which individuals belong to that category due to the highly personalized nature of discussing sexuality and sexual behavior of patients.
Screening
With the discovery of Treponema pallidum, the effective diagnostic test known as Wassermann test was developed in 1906. However, in order to diagnose the diseases, the complexities continue to challenge the clinicians.
The serological tests with the detection of antibodies against T.pallidum, remain the most reliable form of diagnosis of syphilis, regardless of the stage of infection. Historically, the initial test was a complement fixation test and the antigen was from the liver of an infant who died of congenital syphilis. The common nontreponemal (NTT) screening tests include the venereal disease research laboratory (VDRL) and the Rapid Plasma Reagin (RPR) which was later developed, both of which detects the antibodies among the patients with syphilis. The NTT can commonly detect antibodies as early as 6 days post-infection and are used globally.
Treponemal tests (TT) detect specific anti-treponemal antibodies and have higher sensitivity than the NTT and are used as a confirmatory test for syphilis. The treponemal tests can be reactive for years among individuals either with or without treatment.
The direct detection of Treponema pallidum uses various methods for the direct detection of the microorganisms or their DNA which includes Darkfield microscopy, direct fluorescent antibody test for T.pallidum (DFA-TP) in the blood fluids, direct test for T.pallidum in tissue sections, Rabbit infectivity Test (RIT) and Polymerase chain reaction (PCR).
Prenatal syphilis screening and congenital syphilis
Congenital syphilis presents as two clinical syndromes; early (diagnosed during the first 2 years) and late (after 2 years of life). The prevention of the congenital syphilis is based on identifying the disease among pregnant women with the initial screening done in the first trimester and repeated at 28 weeks and also among women in high risk of acquiring the disease such as sex trade workers. This screening can prevent the transmission of the disease from the mother to the fetus by treating the mother in pregnancy. However, the detection at near term or at delivery can help with the early treatment of the disease.
As Syphilis appears to be on the rise, particularly affecting the MSM population and infants, screening for syphilis in high-risk populations are often recommended. It is also equally essential to understand the sexual behaviors of the patients so counsel, services and appropriate testing can be provided.
Penicillin
Although Penicillin G is the preferred medication used for the treatment of all stages of syphilis, the dosage and the duration is based on the stage and the clinical presentation of the disease. The preparation used for the penicillin is also essential to combat the disease as T.pallidum can thrive in sites that cannot properly be accessed by certain forms of penicillin. In the case of allergic reaction to penicillin, affected individuals will be treated with other antibiotics such as doxycycline.
References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956094/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530970/
- https://www.ncbi.nlm.nih.gov/pubmed/24461955
- https://cvi.asm.org/content/22/2/137
- http://cdn.intechopen.com/pdfs/23788/InTech-Laboratorial_diagnosis_of_syphilis.pdf
- https://www.cdc.gov/std/tg2015/syphilis.htm
- https://www.cdc.gov/std/stats16/Syphilis.htm
- https://jamanetwork.com/journals/jama/fullarticle/183391
- https://cvi.asm.org/content/22/2/137
- https://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/